Reactions which can manipulate the connectivity of the molecular skeleton are
underexplored as tools for late-stage functionalization, in part because their
implementation has been hindered by their often nonintuitive retrosynthetic logic. This
presentation will cover selected transformations discovered in our laboratory which
address this challenge by enabling single-atom changes to aliphatic and aromatic
systems through the insertion and deletion of single heavy atoms (C,N,O, etc.), as well
as more complex manipulations leveraging combinations of these elementary
transformations. Our approach to this problem is modality-agnostic, drawing from a
wide range of reactive species and synthetic disciplines (organometallic chemistry,
reagent design, photochemistry). Applications to late-stage functionalization and
diversification of complex pharmaceutically relevant compounds as well as unique
opportunities for synthesis will be presented alongside mechanistic findings.
Mark Levin (University of Chicago)